T lymphocytes recognize and interact with specific antigens, including tumor-associated or tumor-specific antigens. Because T lymphocytes are able to kill tumor cells, the last 25 years has seen a great deal of interest in targeting tumor cells with T lymphocytes, either antigen-specific T lymphocytes, or T lymphocytes genetically modified to express one or more chimeric antigen receptors (CARs; see, e.g., Eshhar, U.S. Pat. No. 7,741,465; Eshhar, U.S. Patent Application Publication No. 2012/0093842). However, given the ability of T lymphocytes to kill not only tumor cells displaying a certain antigen but normal cells displaying the same antigen, it is desirable to incorporate into the T lymphocytes a safety mechanism that enables rapid killing of the cells after administration to a patient should off-target effects prove deleterious to the patient.
While a system to kill T cells has described (Straathof et al. (2005) Blood 105(11):4247-4254), this system was dependent upon specific and difficult-to-make protein modifications, rendering the system undesirable for practical use. As such, there exists a need in the art for a safety system to rapidly kill therapeutic T lymphocytes that are relatively simple and straightforward to construct. T lymphocytes comprising such a safety system are provided herein.